Brain Research 965 (2003) 75–82 www.elsevier.com / locate / brainres Research report Heat nociception is severely reduced in a mutant mouse deficient for the L1 adhesion molecule a, ,1 a ,1 b b * ¨ Jonas Thelin , Alexandra Waldenstrom , Udo Bartsch , Melitta Schachner , a Jens Schouenborg a Section for Neurophysiology, Department of Physiological Sciences, Lund University, BMC F10, S-221 84 Lund, Sweden b ¨ ¨ Zentrum f ur Molekulare Neurobiologie, Universitat Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany Accepted 3 December 2002 Abstract Recent findings indicate that the spatial organization of the spinal nociceptive reflex system is adjusted postnatally through experience-dependent mechanisms. The cellular and molecular mechanisms underlying this tuning are not known. Because the adhesion molecule L1 is known to play an important role in neural development and synaptic plasticity, we studied the nociceptive withdrawal reflexes in awake adult mutant mice deficient in L1. Withdrawal reflexes were elicited by a CO laser (heat stimulation) and von Frey 2 monofilaments (tactile stimulation). L1-deficient mice ( n510) had an abnormally high nociceptive heat-reflex threshold compared with wild-type mice ( n511), except for the nose. Other behavioral signs of heat pain, such as vocalization, were either absent or strongly reduced in L1-deficient mice. Tactile thresholds for withdrawal reflexes were increased in L1-deficient mice when compared with wild-types except for the tail. By contrast, the spatial organization of the withdrawal reflexes appeared normal indicating that the L1 adhesion molecule is not essential for the spatial adjustments of reflex connections during development. The termination patterns of thin primary afferent fibers in the superficial dorsal horn, visualized using intra-plantar injections of WGA-HRP, were normal, suggesting that decreased nociceptive heat sensitivity in L1-deficient mice is mainly due to altered central processing. In view of the known interactions between L1 and some of the NMDA-receptor subtypes, and the prominent role of NMDA receptors in nociception and plasticity, it is conceivable that the hypoalgesia seen in L1 mutants is due, in part, to disturbed NMDA-receptor function.  2003 Elsevier Science B.V. All rights reserved. Theme: Sensory systems Topic: Pain: pathways Keywords: Functional genomic; Pain; NMDA-receptor; Corticospinal tract; Nociceptive withdrawal reflex 1. Introduction adhesion molecules have been shown, in vitro and in vivo, to be involved directly or indirectly in synaptic plasticity Adhesion molecules have recently been recognized as (for reviews see Refs. [30,33]). One adhesion molecule important not only during ontogenesis of the nervous participating in synaptic plasticity is the neural recognition system, but also in the adult nervous system undergoing molecule L1 [27]. L1 is a transmembrane glycoprotein of regeneration after lesions. Furthermore, the expression of the immunoglobulin (Ig) superfamily, and consists of six adhesion molecules is altered in animals that have memor- immunoglobulin-like domains, five fibronectin type III-like ized objects [13,38] and interference with adhesion mole- repeats, a single-pass transmembrane domain, and a short, cule function modifies memory function [39,43]. Several phylogenetically highly conserved cytoplasmic tail [29]. The protein serves important functions in the developing and adult nervous systems, and is involved in such diverse *Corresponding author. Tel.: 146-46-222-4651; fax: 146-46-222- processes as nerve cell migration, axonal outgrowth and 7756. fasciculation, neuronal survival, axonal regeneration, and E-mail address: jonas.thelin@mphy.lu.se (J. Thelin). 1 These authors have contributed equally to the study. synaptic plasticity [3,20]. 0006-8993 / 02 / $ – see front matter  2003 Elsevier Science B.V. All rights reserved. doi:10.1016 / S0006-8993(02)04126-4